Linked Life Data

15972635

Source:http://linkedlifedata.com/resource/pubmed/id/15972635

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-6-23
pubmed:abstractText
We investigated the role of aryl hydrocarbon receptor (AhR) in the regulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced apoptosis in thymic T cells. AhR knockout (KO) mice were resistant to TCDD-induced thymic atrophy and apoptosis when compared with the AhR wild-type mice. TCDD triggered the expression of several apoptotic genes, including FasL in AhR wild-type but not AhRKO mice. TCDD-induced increase in FasL was seen only in thymic stromal but not thymic T cells. When TCDD-exposed stromal cells were mixed with untreated thymic T cells, increased apoptosis was detected in T cells that involved Fas-FasL interactions. Thus, apoptosis in T cells was not detected when TCDD-treated stromal cells from FasL-defective or AhRKO mice were mixed with wild-type T cells or when TCDD-exposed wild-type stromal cells were mixed with Fas-deficient T cells. TCDD treatment, in vivo and in vitro, led to colocalization and translocation of NF-kappaB subunits (p50, p65) to the nucleus in stromal but not T cells from AhR wild-type mice. NF-kappaB activation was not observed in stromal cells isolated from TCDD-treated AhRKO mice. Mutations in NF-kappaB-binding sites on the FasL promoter showed that TCDD regulates FasL promoter activity through NF-kappaB. TCDD treatment in vivo caused activation of the death receptor and mitochondrial pathways of apoptosis. Cross-talk between the two pathways was not necessary for apoptosis inasmuch as TCDD-treated Bid KO mice showed thymic atrophy and increased apoptosis, similar to the wild-type mice. These findings demonstrate that AhR regulates FasL and NF-kappaB in stromal cells, which in turn plays a critical role in initiating apoptosis in thymic T cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
175
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
90-103
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15972635-Active Transport, Cell Nucleus, pubmed-meshheading:15972635-Animals, pubmed-meshheading:15972635-Apoptosis, pubmed-meshheading:15972635-Base Sequence, pubmed-meshheading:15972635-Coculture Techniques, pubmed-meshheading:15972635-DNA, pubmed-meshheading:15972635-Fas Ligand Protein, pubmed-meshheading:15972635-Female, pubmed-meshheading:15972635-Male, pubmed-meshheading:15972635-Membrane Glycoproteins, pubmed-meshheading:15972635-Mice, pubmed-meshheading:15972635-Mice, Inbred C57BL, pubmed-meshheading:15972635-Mice, Knockout, pubmed-meshheading:15972635-Models, Biological, pubmed-meshheading:15972635-Molecular Sequence Data, pubmed-meshheading:15972635-NF-kappa B, pubmed-meshheading:15972635-Phenotype, pubmed-meshheading:15972635-Promoter Regions, Genetic, pubmed-meshheading:15972635-RNA, Messenger, pubmed-meshheading:15972635-Receptors, Aryl Hydrocarbon, pubmed-meshheading:15972635-Stromal Cells, pubmed-meshheading:15972635-T-Lymphocytes, pubmed-meshheading:15972635-Tetrachlorodibenzodioxin, pubmed-meshheading:15972635-Thymus Gland
pubmed:year
2005
pubmed:articleTitle
Treatment of mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin leads to aryl hydrocarbon receptor-dependent nuclear translocation of NF-kappaB and expression of Fas ligand in thymic stromal cells and consequent apoptosis in T cells.
pubmed:affiliation
Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural